en Infectious Disease Infectious Disease Original Research Original Research <strong>Background: </strong>The COVID-19 infection is a novel virus without any specific targeted therapies; thus, focusing on primary epidemiologic concerns, preventive strategies, risk factors, exacerbation factors, and mortality-related factors are of great importance to better control this disorder. There are some controversies about the factors associated with COVID-19 in different theories, and addiction is no exception.<br> <strong>&nbsp;&nbsp; Methods:</strong> We conducted a large cross-sectional study of 513 hospitalized Iranian patients with COVID-19 infection to evaluate the severity of disease courses in patients with or without history of opium addiction. We recorded these data retrospectively after patients&rsquo; discharge from the hospital. For the quantitative data, we used independent-samples t and Mann-Whitney tests. The qualitative data were calculated using Fisher exact and chi-square tests in IBM SPSS Statistics Version 22. Also, p<0.05 was considered statistically significant.<br> <strong>&nbsp;&nbsp; Results: </strong>There was no significant difference regarding mean days of hospitalization in opium positive and negative groups (7.95&plusmn;8.39 vs 8.35&plusmn;5.11, respectively) (p=0.771); however, the need for intensive care unit (ICU) admission was significantly higher in the opium positive group (36% vs 11%) (p=0.005). The mean days of ICU stay was significantly higher in the opium positive group (2.36&plusmn;3.81 vs 0.86&plusmn;2.90) (p=0.026). The percentage of febrile patients, anosmia/hyposmia, and dysgeusia at the initiation of hospitalization was significantly lower in the opium positive group (39% vs 66%; 8% vs 23%; 8% vs; 20%, respectively) (p=0.002, 0.018, and .031, respectively). In the laboratory tests, only the white blood cell (WBC) count and the segmented cells were higher in the opium positive group (10.1&plusmn;6.60 vs 7.38&plusmn;4.14 and 73&plusmn;20.47 vs 56.5&plusmn;32.60, respectively) (p=0.018 and .001, respectively) and lymphocytes were lower in the opium positive (15.60&plusmn;8.25 vs18.70&plusmn;10.12) (p=0.048). Opium addicts had a significantly lower rate of azithromycin and lopinavir/ritonavir prescription in their initiation therapy (19% vs 34%, and 47% vs 70%, respectively) (p=0.038 and 0.012, respectively).<br> <strong>&nbsp;&nbsp; Conclusion:</strong> Opium addict patients with COVID infection may be more febrile and experience more disease-specific symptoms and more severe disease course. These patients may show more evidence of laboratory inflammation and probable superinfections, so may manage with more caution and somehow different therapeutic regimen. Corona, COVID-19, SARS-CoV-2, Opium, Substance, Addiction, Drug Abuse, Severity, Outcome 870 874 http://mjiri.iums.ac.ir/browse.php?a_code=A-10-3072-5&slc_lang=en&sid=1 Taghi Riahi riahi.t@iums.ac.ir 200319475328460065120 200319475328460065120 No Department of Internal Medicine, School of Medicine, Rasool Akram Medical Complex, Iran University of Medical Sciences, Tehran, Iran Afsaneh Sadeghzadeh-Bazargan sadeghzadeh.a@iums.ac.ir 200319475328460065121 200319475328460065121 Yes Department of Dermatology, Rasool Akram Medical Complex, Iran University of Medical Sciences, Tehran, Iran Sima Shokri shokri.s@iums.ac.ir 200319475328460065122 200319475328460065122 No Department of Allergy and Clinical Immunology, Rasool Akram Medical Complex, Iran University of Medical Sciences, Tehran, Iran Davoud Ahmadvand d.ahmadvand@iums.ac.ir 200319475328460065123 200319475328460065123 No Department of Medical Laboratory Sciences, School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran Babak Hassanlouei hasanlooei.b@iums.ac.ir 200319475328460065124 200319475328460065124 No Department of Epidemiology, School of Public Health, Iran University of Medical Sciences, Tehran, Iran Amir Baghestani amir0baghestani@gmail.com 200319475328460065125 200319475328460065125 No Department of General Medicine, Rasool Akram Medical Complex, Iran University of Medical Sciences, Tehran, Iran Ali Khazaeian Dr.a.khazaeian@gmail.com 200319475328460065126 200319475328460065126 No 6. Department of General Medicine, Rasool Akram Medical Complex, Iran University of Medical Sciences, Tehran, Iran Forough Seifi Gharabaghloo seifi.forough@yahoo.com 200319475328460065127 200319475328460065127 No Department of General Medicine, Rasool Akram Medical Complex, Iran University of Medical Sciences, Tehran, Iran Morteza Hassanzadeh hassanzadeh.m@iums.ac.ir 200319475328460065128 200319475328460065128 No Department of Internal Medicine, School of Medicine, Rasool Akram Medical Complex, Iran University of Medical Sciences, Tehran, Iran Azadeh Goodarzi goodarzi.a@iums.ac.ir 200319475328460065129 200319475328460065129 No Department of Dermatology, Rasool Akram Medical Complex, Iran University of Medical Sciences, Tehran, Iran